AChE Inhibitor

Merulinic acid (Geranicardic acid) is an acetylcholinesterase (AChE) inhibitor with an IC₅₀ >94 μM against electric eel-derived AChE. Merulinic acid can be used for the research of alzheimer’s disease.

hAChE-IN-3 (compounds 5c) is a potent and blood-brain barrier permeable AChE, BuChE， MAO-B-IN-1 and BACE-1 inhibitor, with IC₅₀ values of 0.44, 0.08, 5.15 and 0.38 μM, respectively. hAChE-IN-3 has antioxidant activity and metal chelating ability. In addition, hAChE-IN-3 can bind to peripheral anion sites, and affect β amyloid and reduce Alzheimer's-associated neurodegeneration. hAChE-IN-3 has the potential for the research of Alzheimer's disease.

AChE/PDE4-IN-1 (compound 12c) is a potent and selective dual PDE4/AChE inhibitor, with IC₅₀s of 0.28 μM and 1.88 μM for AChE and PDE4D, respectively. AChE/PDE4-IN-1 exhibits anti-neuroinflammatory effect for the research of Alzheimer's disease.

Cubebin ((-)-Cubebin), a dibenzyl butyrolactone lignan, is an orally active AChE inhibitor. Cubebin binds to active sites of NF-κB, TNF-α, and TGF-β1 via hydrogen and hydrophobic interactions, obstructing critical residues to inhibit pro-inflammatory or renal fibrosis-related activity. Cubebin enhances p38 MAPK phosphorylation to increase tyrosinase gene expression, stimulating melanogenesis via elevated tyrosinase activity, expression, and mRNA levels. Cubebin reduces oxidative stress via enhanced endogenous antioxidant enzyme activity and inhibited lipid peroxidation, regulates lipid metabolism, improves glycemic control, and exerts renoprotective effects via reduced renal dysfunction markers and improved renal architecture. Cubebin shows antimicrobial activity. Cubebin exerts larvicidal activity against Angiostrongylus cantonensis larvae, with no cytotoxicity toward monkey or human cell lines or Caenorhabditis elegans. Cubebin can be used for the research of diabetic nephropathy, melanoma, colon adenocarcinoma, neuroangiostrongyliasis, Alzheimer’s disease (AD) and depression.

AChE/BuChE-IN-9 is a dual Cholinesterase inhibitor that acts on electric eel acetylcholinesterase (AChE) (IC₅₀ = 14.82 μM) and horse serum butyrylcholinesterase (IC₅₀ = 27.91 μM) through non-competitive and mixed-mode inhibition, respectively. AChE/BuChE-IN-9 can be used for research on Alzheimer's disease.

α-Amylase/α-Glucosidase-IN-7 (Compound 3f) is a competitive α-glucosidase and α-amylase enzyme inhibitor with IC₅₀ values of 18.52 and 20.25 µM, respectively. α-Amylase/α-Glucosidase-IN-7 can also effectively inhibit AChE and BChE, with IC₅₀ values of 9.25 and 10.06 µM respectively. α-Amylase/α-Glucosidase-IN-7 can be used in diabetes and Alzheimer’s research.

hAChE-IN-1 (Compound 24) is a potent hAChE inhibitor with an IC₅₀ of 1.09 μM. hAChE-IN-1 inhibits tau-oligomerization with an EC₅₀ of 2.71 μM in cellular tau FRET assay.

AChE-IN-63 (Compound 5AD) is a selective inhibitor of hAChE (IC₅₀=0.103 μM). AChE-IN-63 also inhibits hBChE and hBACE-1 (IC₅₀= 10 μM (hBChE); 1.342 μM (hBACE-1)). AChE-IN-63 inhibits Aβ aggregation, preventing the formation and deposition of Aβ1-42. AChE-IN-63 can effectively penetrate the blood-brain barrier and is orally effective. It is primarily used in Alzheimer's disease research.

AChE-IN-112 is an acetylcholinesterase (AChE) inhibitor with an IC₅₀ of 0.41 μM. AChE-IN-112 scavenges various reactive oxygen and reactive nitrogen species, including DPPH, ABTS, NO, hydroxyl and hydrogen peroxide free radicals. AChE-IN-112 can be used for the research of Alzheimer's disease.

Methyl isoplatydesmine is a cholinesterase inhibitor with spasmolytic activity, with a K_i value of 30.0 μM against electric eel acetylcholinesterase and a K_i value of 19.0 μM against horse serum butyrylcholinesterase. Methyl isoplatydesmine mediates spasmolytic activity by blocking voltage-dependent calcium channels. Methyl isoplatydesmine can be used in the research of Alzheimer's disease and related dementias.

2-Acetoxyacorenone (compound 8) is a sesquiterpenoid, which can be isolated from the rhizome of Acorus tatarinowii. 2-Acetoxyacorenone has potent AChE and β-BACE1 inhibitory activity and can be used in the study of Alzheimer's disease.

Stacofylline hydrochloride (S 9977), a Xanthine (HY-W017389) derivative, is a potent AChE inhibitor with an IC₅₀ of 5-50 nM. Stacofylline shows anti-amnesic and promnesic activities.

AChE-IN-108 is a potent mixed-type acetylcholinesterase (AChE) inhibitor with an in vitro IC₅₀ of 0.17 nM. AChE-IN-108 acts on both free AChE and the enzyme-substrate complex to exert mixed-type inhibition. AChE-IN-108 can be used for the study of acetylcholinesterase inhibition in Alzheimer’s disease (AD).

AChE-IN-119 is a selective acetylcholinesterase (AChE) inhibitor with an IC₅₀ of 0.0641 μM and a K_i of 0.01648 μM. AChE-IN-119 exerts antioxidant effects by scavenging DPPH free radicals. AChE-IN-119 exhibits mixed-type inhibition and interacts with both the catalytic active site and the peripheral anionic site of acetylcholinesterase. AChE-IN-119 can be used for the research of Alzheimer's disease.

AChE/BChE/MAO-A-IN-2 is an AChE, BChE, and MAO-A inhibitor with IC₅₀ values of 104.28 nM, 23.04 nM, and 215.50 nM, respectively. AChE/BChE/MAO-A-IN-2 exhibits selective antiproliferative activity against cancer cells and low toxicity toward normal cells. AChE/BChE/MAO-A-IN-2 can be used for the research of alzheimer's disease, neuroblastoma.

MTAAAR is a polypeptide obtained from the enzymatic hydrolysis of C-phycocyanin (HY-D1025) and possesses neuroprotective activity. MTAAAR enhances the activities of antioxidant enzymes SOD, CAT, and GSH-Px, reduces ROS, inhibits apoptosis and acetylcholinesterase (AChE) activity in brain tissue, and decreases protein carbonyl content. In the MPTP (HY-W114750)-induced zebrafish Parkinson's disease model, MTAAAR exhibits antioxidant effects, inhibits autophagy and apoptosis, reverses the loss of dopaminergic neurons and cerebral blood vessels, and alleviates motor deficits. MTAAAR can be used for research on Parkinson's disease.

AChE/MAO-B-IN-9 (Compound E12) is an orally active, selective, reversible, non-competitive AChE and MAO-B inhibitor, with an IC₅₀ of 0.156 μM against electric eel AChE. AChE/MAO-B-IN-9 inhibits Aβ40/42 fibril formation, promotes Aβ fibril depolymerization, and inhibits Tau protein fibril formation. AChE/MAO-B-IN-9 exerts antioxidant and neuroprotective effects, and improves scopolamine (HY-N0296)-induced memory impairment in mice. AChE/MAO-B-IN-9 can be used for the research of Alzheimer's disease.

AChE-IN-88 (Compound 26) is a novel pyridazine derivative. AChE-IN-88 is an orally active multi-target ligand for Alzheimer's disease (AD) that inhibits both acetylcholinesterase (AChE) and amyloid β protein (Aβ) aggregation (pIC₅₀: 7.16).

AChE-IN-104 (compound 3e) is a potent acetylcholinesterase (AChE) inhibitor with an IC₅₀ of 8.01 µM. AChE-IN-104 also inhibits BChE and MAO-A with IC₅₀s of 65.41 µM and 1.51 µM, respectively. AChE-IN-104 can be used for Alzheimer’s disease (AD) research.

AChE-IN-20 (compound M26) is a potent AChE inhibitor with IC₅₀ value of 397.32 nM and with K_i value of 335.76 nM. AChE-IN-20 shows inhibition potency against hCA I , hCA II and α-GLY with IC₅₀ values of 84.14, 69.24 and 52.08 nM and with K_i values of 97.86, 76.23 and 57.93 nM, respectively.